Cervical cancer etiology is better understood than the origins of most major malignancies. Within the Division of Cancer Epidemiology and Genetics, several groups continue to study the most interesting and important research topics. In the HPV Guanacaste Study and the ALTS project, remaining topics in natural history of the causal virus (human papillomavirus, HPV) are the focus, as well as new methods comparisons. The unusually high prevalence of HPV in sub Saharan Africa is the focus in the Nigeria Project Itoju. Cervical Visualization Project: In this set of studies, HPV natural history is assessed visually (using a web-based open-source software system developed with the National Library of Medicine), microscopically (cytology and histology) and using a variety of molecular biomarkers. HPV Genome Project. Viral genomic studies are designed to determine why certain types of HPV, if persistent, are extremely powerful carcinogens (acquired genetic syndromes with high penetrance) while related HPV types are not. In the HPV Methylation Project, we are exploring the epigenetic changes in HPV and host genes in relationship to risk of HPV persistence, progression to CIN3, and invasion.The Persistence and Progression (PaP) cohort is a collaboration with Kaiser Permanente Northern California. More than 40,000 women with dual testing with positive HPV DNA assays and cytology are being followed for outcome. This is the main source of specimens for our studies of HPV genome, epigenetics, and microbiome.The New Mexico Pap Registry is a collaboration with Dr. Cosette Wheeler at U. New Mexico, consisting of a statewide surveillance of cytology and histology outcomes. In a subset, HPV testing is available. The goal eventually is to monitor the impact of HPV vaccination on cervical screening.HPV Cervical Cancer Risk Prediction. This study involves translation of what we have learned about HPV and cervical carcinogenesis into clinical guidelines, particularly via risk prediction models. The main source of data is Kaiser Permanente Northern California, with its decade-long experience with HPV and Pap cotesting.Of note, these studies are intrinsically related to HIV as well. Cervical cancer is an AIDS-defining condition, and there are many links between HIV and HPV. HPV prevalence is profoundly increased in HIV-immunosuppressed women, and our analyses take into account HIV status. The impact of HIV on HPV might be HPV type-specific, giving clues to type-specific immune responses. On the other hand, treatment for cervical cancer and its precursor lesions is destructive and may increase risk of HIV transmission in the healing period if sexual intercourse with an infected partner occurs; this is of great importance to possible HPV screen-and-treat strategies in low-resource regions especially sub-Saharan Africa (GAVI countries).This research project is human population based, and both etiologic and translational.